Ovarian cancer is second only to breast cancer as the most common cause of death from gynecological malignancy in women in this country. The principal objective of this project is to identify antigens or markers of ovarian tumors which can be used in an immunodiagnostic assay for the detection of early ovarian cancer. Xenogeneic sera will be used to identify (1) antigens in extracts of ovarian tumors and (2) cell surface and shed antigens of cultured ovarian tumor cell lines. Using rabbit antisera we have already identified two antigens (OvC-1 and OvC-2) present in ovarian tumors but not in normal ovaries. Both these antigens are present in amniotic fluid which is a convenient source of material for isolation of the antigens. OvC-1 is a new pregnancy-associated antigen. OvC-2 is a new oncofetal antigen and is found in a fetal intestine as well as in ovarian tumors. The development of sensitive assays (e.g. radioimmunoassays) capable of detecting these antigens in serum or plasma will enable us to determine their possible usefulness for the immunodiagnosis of ovarian cancer. Cultured ovarian tumor cells will be used in attempts to identify new antigens not previously identified when tumor extracts were used. Components shed from cultured ovarian tumor cells will also be studied. Antisera to the cultured cells and their released components will be raised in rabbits and monoclonal antibodies will be produced using the procedure of Kohler and Milstein. The specificity of the antisera will be studied by serological techniques using binding or adherence assays and by radioimmunoprecipitation. New antigens showing ovarian tumor specificity will be examined for their possible use in the early detection of ovarian cancer.